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A Synthetic Biology Approach To Engineering New Anticancer Agents, Shane Robert Wesener

Theses and Dissertations

Histone deacetylase (HDAC) inhibitors are becoming increasingly valuable therapeutic agents in treatment of several types of malignancies. FK228 is a depsipeptde anticancer compound produced by Chromobacterium violaceum no. 968 through a nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) hybrid assembly line. In the present study, reconstitution of the biosynthetic pathway responsible for the production of FK228 revealed cross-talk between modular PKS and fatty acid synthase. This pathway contains two PKS modules on the DepBC enzymes that lack a functional acyltransferase (AT) domain, and no apparent AT-encoding gene exists within the gene cluster or its vicinity. We reported through heterologous expression of …